chr19-41005898-C-G

Variant names:

• chr19-41005898-C-G
• rs4803418
• NM_000767.5:c.485-1007C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.485-1007C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,798 control chromosomes in the GnomAD database, including 6,517 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6517 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 23 publications found

Genes affected

CYP2B6 (HGNC:2615): (cytochrome P450 family 2 subfamily B member 6) This gene, CYP2B6, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide. Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000767.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	NM_000767.5	MANE Select	c.485-1007C>G		intron	N/A	NP_000758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	ENST00000324071.10	TSL:1 MANE Select	c.485-1007C>G		intron	N/A	ENSP00000324648.2
	CYP2B6	ENST00000593831.1	TSL:2	c.256+1452C>G		intron	N/A	ENSP00000470582.1
	CYP2B6	ENST00000594187.1	TSL:5	n.69-1007C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41579 AN: 151680 Hom.: 6517 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41596 AN: 151798 Hom.: 6517 Cov.: 31 AF XY: 0.281 AC XY: 20833 AN XY: 74184

African (AFR) AF: 0.124 AC: 5148 AN: 41354

American (AMR) AF: 0.352 AC: 5363 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2309 AN: 5158

South Asian (SAS) AF: 0.347 AC: 1667 AN: 4806

European-Finnish (FIN) AF: 0.374 AC: 3937 AN: 10526

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21110 AN: 67936

Other (OTH) AF: 0.286 AC: 604 AN: 2110

Alfa AF: 0.292 Hom.: 883

Bravo AF: 0.267

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.82
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4803418; hg19: chr19-41511803;